ArticleNature communications2024
Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58citing papers in PubMed
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58 citing papers in PubMed.
- Identification of Diagnostic Biomarkers Among Metabolism-related Genes in Rheumatoid Arthritis: Insights into Immune Landscape and Molecular Subtype Characterization.Applied biochemistry and biotechnology · 2026Article
- Nonlinear Correlation Between Prognostic Nutritional Index and Disease Activity of Rheumatoid Arthritis: A Cross-Sectional Study.Immunity, inflammation and disease · 2026Article
- Immune-mediated rheumatoid arthritis: from single-cell genomics to new therapies.Nature immunology · 2026Review
- Specificity, frequency, and phenotype of citrullinated-specific T cells vary with disease activity in rheumatoid arthritis.JCI insight · 2026Article
- Beyond B cell helpers: diverse roles of peripheral helper T cells.International immunology · 2026Review
- Optimization of the Isolation and Purification of Formononetin fromPlants (Basel, Switzerland) · 2026Article
- Bioinformatics analysis reveals shared gene signatures and molecular mechanisms between periodontitis and rheumatoid arthritis in the context of aging.Acta odontologica Scandinavica · 2026Article
- Age-Associated B Cells: Origins, Regulation, and Tissue-Specific Pathogenic Contributions in Autoimmune, Metabolic, and Neurological Diseases.Immunological reviews · 2026Review
- Article
- Granzyme K CD8⁺ T cells with tissue-resident features promote intestinal inflammation in patients with Crohn's disease.Experimental & molecular medicine · 2026Article
- Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.Nature immunology · 2026Article
- B Cells or T Cells in the Development and Sustenance of Rheumatoid Arthritis: Who is the Potential Contributor?Mediterranean journal of rheumatology · 2026Review
- Inflammation-Driven Lymphoid Structures: Organization, Function, and Clinical Impact Across Autoimmunity, Cancer, and Checkpoint Toxicity.Immunological reviews · 2026Review
- Early and late RNA eQTL are driven by different genetic mechanisms.Nature communications · 2026Article
- Medical software for precision diagnostics of infection with immunoprofiling and artificial intelligence.Journal of translational medicine · 2026Review
- Single-cell and spatial profiling of peripheral blood and synovium unveils pro-arthritis CNBPJournal of translational medicine · 2026Article
- Longitudinal peripheral blood multi-omic profiling in seropositive individuals identifies immune endotypes and predictive models for future rheumatoid arthritis conversion.medRxiv : the preprint server for health sciences · 2026Article
- Epstein-Barr Virus Infection at Single-Cell Resolution.Journal of medical virology · 2026Review
- Multi-Targeted Therapeutic Mechanisms of Huangqi Guizhi Wuwu Decoction Against Rheumatoid Arthritis: An Integrated Approach Combining Serum Pharmacochemistry, Network Pharmacology, Metabolomics, and Experimental Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
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Authors and funding
27 authors.
Garrett Dunlap *Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2627-0506
Aaron Wagner *Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Nida Meednu *Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA.ORCID http://orcid.org/0000-0002-2868-3339
Ruoqiao WangDepartment of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.ORCID http://orcid.org/0000-0003-2013-4850
Fan ZhangDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6102-2970
Jabea Cyril EkabeDivision of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA.
Anna Helena JonssonDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9558-2474
Kevin WeiDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1821-167X
Saori SakaueDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3618-9717
Aparna NathanDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5975-2851
Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network
Vivian P BykerkHospital for Special Surgery, New York, NY, USA.
Laura T DonlinHospital for Special Surgery, New York, NY, USA.ORCID http://orcid.org/0000-0002-1428-090X
Susan M GoodmanHospital for Special Surgery, New York, NY, USA.ORCID http://orcid.org/0000-0003-1197-7864
Gary S FiresteinDivision of Rheumatology, Allergy and Immunology, University of California, San Diego;, La Jolla, CA, USA.
David L BoyleDivision of Rheumatology, Allergy and Immunology, University of California, San Diego;, La Jolla, CA, USA.
V Michael HolersDivision of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-5634-7746
Larry W MorelandDivision of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA.
Darren TabechianDivision of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA.
Costantino PitzalisCentre for Experimental Medicine & Rheumatology, EULAR Centre of Excellence, William Harvey Research Institute, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0003-1326-5051
Andrew FilerRheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK.ORCID http://orcid.org/0000-0001-8164-6249
Soumya RaychaudhuriDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1901-8265
Michael B BrennerDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6202-8445
Juilee ThakarDepartment of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.ORCID http://orcid.org/0000-0003-4479-4183
Andrew McDavidDepartment of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Deepak A RaoDivision of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. darao@bwh.harvard.edu.ORCID http://orcid.org/0000-0001-9672-7746
Jennifer H AnolikDivision of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA. jennifer_anolik@urmc.rochester.edu.ORCID http://orcid.org/0000-0002-1450-1549
Funding
Role of fibroblastic stromal cells and notch signaling in tissue inflammation in RA and SLEP01AI148102 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Betty Diamond · 2021 to 2026
$17.3MPEARL: Pathway Exploration and Analysis in Renal LupusUH2AR067688 · NIAMS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI DIAMOND, BETTY, WOFSY, DAVID · 2014 to 2020
$9.0MTissue Acquisition Research GroupUM2AR067678 · NIAMS · STANFORD UNIVERSITY · PI HOLERS, VERNON MICHAEL, UTZ, PAUL JOSEPH · 2014 to 2020
$8.2MPain and synovial pathotypes in AMP AIMUC2AR081025 · NIAMS · UNIVERSITY OF ROCHESTER · PI Jennifer Howitt Anolik, Laura T. Donlin · 2022 to 2026
$7.2MMulti-Ethnic Translational Research Optimization (METRO) Lupus ConsortiumUH2AR067689 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BUYON, JILL P, PUTTERMAN, CHAIM · 2014 to 2020
$6.3MEvolving Adaptive and Effector Mechanisms from Pre-RA Through Established DiseaseUH2AR067681 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 2014 to 2020
$5.5MDiscovery and Functional Impact of Common and Rare Variants in RAR01AR063759 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Soumya Raychaudhuri · 2013 to 2026
$5.4MMolecular and Cellular Dissection of Early Rheumatoid ArthritisUH2AR067694 · NIAMS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI BRENNER, MICHAEL B., GREGERSEN, PETER K. · 2014 to 2020
$5.4MRA-SLE Molecular Deconstruction Leadership CenterUH2AR067677 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2014 to 2020
$4.3MCellular Dynamics at the Synovium-Bone interface in RAUH2AR067690 · NIAMS · UNIVERSITY OF ROCHESTER · PI ANOLIK, JENNIFER HOWITT · 2014 to 2020
$3.0MStanford Technology Accelerating Medicines Partnership CenterUH2AR067676 · NIAMS · STANFORD UNIVERSITY · PI ROBINSON, WILLIAM H, UTZ, PAUL JOSEPH · 2014 to 2020
$2.6MRole of T-bet B cells in rheumatoid arthritisR01AI175212 · NIAID · UNIVERSITY OF ROCHESTER · PI Jennifer Howitt Anolik, Javier Rangel-Moreno · 2024 to 2026
$2.1MNIAID NIH HHS P01 AI148102NIAID NIH HHS R01 AI175212NIAMS NIH HHS K08 AR081412NIAMS NIH HHS R01 AR063759NIAMS NIH HHS R21 AR071670NIAMS NIH HHS UC2 AR081025NIAMS NIH HHS UH2 AR067676NIAMS NIH HHS UH2 AR067677NIAMS NIH HHS UH2 AR067679NIAMS NIH HHS UH2 AR067681NIAMS NIH HHS UH2 AR067685NIAMS NIH HHS UH2 AR067688NIAMS NIH HHS UH2 AR067689NIAMS NIH HHS UH2 AR067690NIAMS NIH HHS UH2 AR067691NIAMS NIH HHS UH2 AR067694NIAMS NIH HHS UM2 AR067678
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.
Indexed as
Arthritis, RheumatoidB-LymphocytesSynovial MembraneAdultAgedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleHumansLymphocyte ActivationLymphocyte SubsetsMaleMiddle AgedPlasma CellsSingle-Cell AnalysisTranscriptome
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